Figure 1.
Invasive measurement of hemodynamic parameters in mice.
Mice were anesthetized with pentobarbital, mechanical ventilation was instituted and mice were ventilated using pressure-controlled settings (inspiratory pressure of 15 mbar, positive end-exspiratory pressure 5 mbar, 60% inspired oxygen concentration). The common carotid artery was cannulated utilizing a polyethylene tube. The arterial catheter was connected to a pressure transducer which automatically calculated the HR by analyzing the amplitude of the pressure signal. For verification of heart measurements, an electrocardiogram (ECG) monitor was connected throughout the experiment. Values were recorded to computer hard drive for further analysis.
Figure 2.
Changes of blood pressure and heart-rate following vascular adenosine injection.
Following insertion of a catheter into the common carotid artery, mean arterial blood pressure and heart rate were measured. Intravascular bolus injection of adenosine as indicated. (A, B) Wild type mice received vehicle (normal saline) or adenosine at indicated doses (100 µl). (C, D) Relative change in mean arterial blood pressure or heart-rate. (A, B: *p<0.05; n = 8; mean±SEM).
Figure 3.
Adenosine bolus injections in gene-targeted mice for the A1AR.
Following insertion of a catheter into the common carotid artery, mean arterial blood pressure and heart rate were measured A1AR−/−-mice received bolus injection of vehicle or indicated doses of adenosine (100 µl) via the carotid artery catheter. (A, B) Heart-rate and blood pressure responses to 100 µg of adenosine compared to wild type mice. (C, D) Relative changes in heart-rate and mean arterial blood pressure. Note: A1AR−/−-mice experience no change in HR following bolus injection of adenosine. (n = 7–8; WT n = 8, *p<0.05 A1AR−/− vs WT; #p<0.05 compared to adenosine-vehicle; mean±SEM;).
Figure 4.
Effect of systemic adenosine administration in AR gene targeted mice.
Following insertion of a catheter into the common carotid artery, mean arterial blood pressure and heart rate were measured. A2AAR−/−, A2BAR−/− orA3AR−/− received bolus injections of vehicle solution or indicated doses of adenosine in 100 µl of vehicle. Change in heart-rate and mean arterial pressure compared to littermate control mice. (A, B) A2AAR−/− (C, D) A2BAR−/− (E, F) A3AR−/− (n = 6–8, *p<0.05 compared to adenosine-vehicle; mean±SEM).
Figure 5.
Effect of A1AR antagonist DPCPX on adenosine-induced slowing of the heart-rate.
Following insertion of a catheter into the common carotid artery, mean arterial blood pressure and heart rate were measured after injection of vehicle or adenosine at indicated doses (volume of 100 µl). All animals received 1 mg/kg of the A1AR antagonist DPCPX (i.p., 30 min prior to the experimental procedure) or vehicle. (A, B) Heart-rate or mean arterial blood pressure at indicated time points. (C, D) Relative changes of heart-rate or mean arterial blood pressure (n = 4, * indicates p<0.05 compared to DPCPX treatment; #indicates p<0.05 compared to adenosine-vehicle injection; mean±SEM).
Figure 6.
Effect of A1 adenosine receptor (AR) antagonist DPCPX in AR gene targeted mice.
Following insertion of a catheter into the common carotid artery, mean arterial blood pressure and heart rate were measured after injection of vehicle or adenosine at indicated doses (volume of 100 µl). All animals received 1 mg/kg of the A1AR antagonist DPCPX (i.p., 30 min prior to the experimental procedure) or vehicle. Relative changes in HR and MAP are displayed. (A, B) A1AAR−/− (C, D) A2AAR−/− (E, F) A2BAR−/− (n = 4;* p<0.05 compared to DPCPX treated mice; #p<0.05 compared to adenosine-vehicle; mean±SEM).